QM/MMGBSA binding free energy calculations¶

Requirements¶

In this case, gmx_MMPBSA requires:

-> Must be defined -- -> Optional, but recommended -- -> Optional

See a detailed list of all the flags in gmx_MMPBSA command line here

Command-line¶

That being said, once you are in the folder containing all files, the command-line will be as follows:

gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ci index.ndx -cg 1 13 -ct com_traj.xtc -lm ligand.mol2 -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

mpirun -np 2 gmx_MMPBSA -O -i mmpbsa.in -cs com.tpr -ci index.ndx -cg 1 13 -ct com_traj.xtc -lm ligand.mol2 -o FINAL_RESULTS_MMPBSA.dat -eo FINAL_RESULTS_MMPBSA.csv

where the mmpbsa.in input file, is a text file containing the following lines:

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Sample input file for QM/MMGBSA calculation
This input file is meant to show only that gmx_MMPBSA works. 
Although, we tried to use the input files as recommended in the
Amber manual, some parameters have been changed to perform more 
expensive calculations in a reasonable amount of time. Feel free 
to change the parameters according to what is better for your system.

&general
sys_name="QM/MMGBSA",
startframe=5,
endframe=14,
PBRadii=2,
forcefields="oldff/leaprc.ff99SB,leaprc.gaff"
/
&gb
igb=1, saltcon=0.150,
ifqnt=1, qm_theory=PM3,

# Residues to be treated with QM can be selected using different approaches. Please, make sure to include at least 
# one residue from both the receptor and ligand in the qm_residues mask when using 'ifqnt'. This requirement is 
# automatically fulfilled when using the within keyword https://groups.google.com/g/gmx_mmpbsa/c/GNb4q4YGCH8

# Residue selection by distance (recommended)
qm_residues="within 4"

## Explicit residue selection
#qm_residues="A/40-41,44,47,78,81-82,85,88,115,118,122,215,218-220,232 B/241"

# Residue selection with amber masks
#com_qmmask="(:44,47,85,88,218&!@N,H,CA,HA,C,O) | :241"
#rec_qmmask="(:44,47,85,88,218&!@N,H,CA,HA,C,O)"
#lig_qmmask=":1"
/

Considerations¶

In this case, a single trajectory (ST) approximation is followed, which means the receptor and ligand structures and trajectories will be obtained from that of the complex. To do so, an MD Structure+mass(db) file (com.tpr), an index file (index.ndx), a trajectory file (com_traj.xtc), and both the receptor and ligand group numbers in the index file (1 13) are needed. A ligand .mol2 file is also needed for generating the ligand topology. The mmpbsa.in input file will contain all the parameters needed for the QM/MMGBSA calculation. 10 frames are going to be used when performing QM/MMGBSA calculation with the igb1 (GB-HCT) model (note that mbondi raddi set PBRadii=2 is used), PM3 method and a salt concentration = 0.15M.

A plain text output file with all the statistics (default: FINAL_RESULTS_MMPBSA.dat) and a CSV-format output file containing all energy terms for every frame in every calculation will be saved. The file name in '-eo' flag will be forced to end in [.csv] (FINAL_RESULTS_MMPBSA.csv in this case). This file is only written when specified on the command-line.